The role of CDK inhibitors in breast cancer therapy

Cyclin D1 and cyclin-dependent protein kinases CDK4/6 are part of RB-pathway which plays a very important role in the regulation of cell cycle progression and cell death.D-type cyclins associate with cdk4 and 6 to phosphorylate the Rb protein.Hyperphosphorylation of Rb promotes the release of the E2F family of transcription factors that then promotes entry into S phase through activation of key target genes.CDK inhibitors are proteins that suppress CDK-cyclin protein kinase activity in the G1 phase of the cell cycle and promote G1 arrest in response to environmental or intracellular signals.A literature search of these topics was performed through PubMed.Results from preclinical and early-stage clinical trials support the efficiency of CDK inhibitors such palbociclib, abemaciclib and ribociclib for the treatment of human cancers -including breast cancer.The first-in-class CDK4/6 inhibitor, which significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for steroid receptor -positive, HER2-negative advanced breast cancer is Palbociclib.Other inhibitors (abemaciclib, ribociclib) are still in clinical trials and are a very promising group of drugs.